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Attend this session at the
2019 ASCO Annual Meeting!


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Poster Discussion Session

Time: Saturday June 1, 3:00 PM to 4:30 PM

Location: E450

Genome-wide cell-free DNA fragmentation profiling for early cancer detection.

Sub-category:
Circulating Biomarkers

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3018

Poster Board Number:
Poster Discussion Session (Board #10)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3018)

Author(s): Alessandro Leal, Stephen Cristiano, Jillian Phallen, Jacob Fiksel, Vilmos Adleff, Daniel C. Bruhm, Sarah Østrup Jensen, Jamie E. Medina, Doreen N. Palsgrove, Noushin Niknafs, Valsamo Anagnostou, Patrick M. Forde, Julie R. Brahmer, Remond Fijneman, Julia S. Johansen, Hans J. Nielsen, Gerrit A. Meijer, Claus Lindbjerg Andersen, Robert B. Scharpf, Victor E. Velculescu; Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Johns Hopkins Medical Institutions, Baltimore, MD; The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Aarhus University Hospital, Aarhus, Denmark; Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark; University of Copenhagen, Hvidovre, Denmark; Department for Molecular Medicine, Aarhus University Hospital/Skejby, Århus N, Denmark

Abstract Disclosures

Abstract:

Background: Analyses of cell-free DNA (cfDNA) in the blood provide a noninvasive diagnostic avenue for patients with cancer. However, cfDNA analyses have largely focused on targeted sequencing of specific genes, and the characteristics of the origins and molecular features of cfDNA are poorly understood. We developed an ultrasensitive approach that allows simultaneous examination of a large number of abnormalities in cfDNA through genome-wide analysis of fragmentation patterns. Methods: We used a machine learning model to examined cfDNA fragmentation profiles of 236 patients with largely localized breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancer and 245 healthy individuals. Estimation of performance was determined by ten-fold cross validation repeated ten times. Results: cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation patterns. The degree of abnormality in fragmentation profiles during therapy closely matched levels of mutant allele fractions in cfDNA as determined using ultra-deep targeted sequencing. The sensitivity of detection ranged from 57% to > 99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cfDNA analyses detected 91% of cancer patients. Conclusions: This effort is the first study to demonstrate genome-wide cell-free DNA fragmentation abnormalities in patients with cancer. Results of these analyses highlight important properties of cfDNA and provide a facile approach for screening, early detection, and monitoring of human cancer.

 
Other Abstracts in this Sub-Category:

 

1. Multimodality liquid biopsy for early monitoring and outcome prediction in first-line metastatic HER2-negative breast cancer: Final results of the prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG)— COMET study.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3019 First Author: Jean-Yves Pierga
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

2. Circulating androgen receptor (AR) gene amplification and resistance to 177Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of a phase II clinical trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3020 First Author: Ugo De Giorgi
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

3. Associations of insulin-like growth factor binding proteins and adiponectin with disease progression and mortality in metastatic colorectal cancer: Results from CALGB/SWOG 80405 (Alliance).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3035 First Author: Brendan John Guercio
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

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